This invention is directed to antibiotic compositions exhibiting synergistic activity against a number of multiple-antibiotic-resistant organisms, and to a method of treating infections caused by such organisms in man and other warm-blooded animals. More particularly this invention is concerned both with synergistic antibiotic compositions containing moxalactam, the 1-oxa .beta.-lactam antibiotic compound of the formula ##STR2## or pharmaceutically acceptable salts thereof and, either tobramycin, amikacin or piperacillin (sodium 6-(D(-)-.alpha.-(4-ethyl-2,3-dioxo-1-piperazinylcarbonylamino)-.alpha.-phe nylacetamido]penicillinate), and with a method of treating infections utilizing the 1-oxa antibiotic compound I in combination with tobramycin, amikacin or piperacillin.
The mutual effect of simultaneously administered antibiotics, exerted on each other and on various pathogenic microorganisms, has been the subject of much research. The literature is replete with reports by investigators whose experiments have shown unambiguously that among previously known antibiotics, either synergism or antagonism may occur. In the case of synergism the antibiotic combination exhibits a marked increase in activity over that which could be predicted as the result of a purely additive effect of the two or more drugs in combination. Both quantitative and qualitative synergistic effects have been observed.
The treatment of infections due to multiple-antibiotic-resistant organisms present a challenge which a number of clinicians have in the past sought to meet through the utilization of synergistic antibiotic combinations. The lower effective minimum inhibitory concentrations (mics) of synergistic combinations of the present invention as well as others against such organisms allow for the treatment of those more difficult infections at lower dosage levels than otherwise possible, thereby lowering the probability of toxicity complications, the time for treatment, and, potentially, the cost of therapy. The present invention therefore constitutes a significant addition to the physician's medicinal armamentarium.
The antibiotic compounds utilized in the present invention are known compounds. Tobramycin and amikacin or their sulfuric acid addition salts are commercially available broad spectrum aminoglycoside antibiotics. Piperacillin is a relatively new penicillin antibiotic compound. Its preparation is described by I. Saikawa et al. in the Journal of the Pharmaceutical Society of Japan, 597, No. 9, p 980-986 (1977). The 1-oxa .beta.-lactam compound designated by formula I above was recently described in U.S. Pat. No. 4,138,486, issued Feb. 6, 1979.